Biodegradable polymers are useful in many medical applications, especially drug delivery devices. Many of the biodegradable polymers used are of the thermoplastic type. Polymers made of thermoplastic resins typically liquify or soften at elevated temperatures and resolidify upon cooling. This type of polymer is generally formed into the desired structure for use as sutures, surgical clips, staples, implants, and the like, prior to insertion into the body. Once inserted into the body, these polymers retain their shape.
For drug delivery devices, the drug is generally incorporated into the polymeric composition and formed into the desired shape outside the body. This solid implant is then typically inserted into the body of a human, animal, bird, and the like through an incision. Alternatively, small discrete particles composed of these polymers can be injected into the body by a syringe. Preferably, however, certain of these polymers can be injected via syringe as a liquid polymeric composition.
Liquid polymeric compositions for use as biodegradable controlled release drug delivery systems are described in U.S. Pat. No. 4,938,763, issued to Dunn et al. These compositions are administered to the body in a liquid state or, alternatively, as a solution, typically via syringe. Once in the body the composition coagulates or cures into a solid. One type of polymeric composition consists of a nonreactive thermoplastic polymer or copolymer dissolved in a water-miscible solvent. This polymeric solution is placed into the body where the polymer congeals or precipitatively solidifies upon the dissipation or diffusion of the solvent into the surrounding body tissues.
The presence of a plasticizer within a sustained release composition is known to advance or speed up the release of bioactive material by the sustained release polymer. Known plasticizers have been used to enhance the delivery of drugs from diffusional therapeutic systems. For example, K. Juni et al., Chem. Pharm. Bull., 33, 1609 (1985) disclose that the release rate of bleomycin from polylactic acid microspheres is greatly enhanced by incorporating fatty acid esters into the microspheres. U.S. Pat. No. 4,127,127, issued to Wong et al., discloses systems made from films of segmented copolyesters of butylene terephthalate and polyalkylene ether terephthalate that incorporate plasticizers to create a more diffusible system. Water-insoluble liquid plasticizers are used to "soften" the copolyester and cause its diffusion coefficient to increase, thereby enhancing the diffusion of nonionic drugs. Water-soluble plasticizers are used to create a water-swollen microporous structure, by leaching slowly from the copolyester, to make the composition more permeable to drugs.
Although the liquid polymeric systems as described by Dunn et al. have proven to be beneficial in many respects, they do not enable variable control of release rate, especially control such that the rate is slower. Consequently, there is the need for a liquid composition in which the rate of drug delivery can be more readily controlled especially for a drug that requires longer term release.
It is, therefore, an object of the present invention to provide an improved composition comprising a biodegradable or bioerodible polymer for use as an implant in the body of a human, bird, fish, etc. Another object is to provide an improved polymeric composition for a diffusional therapeutic delivery system that can be administered to an implant site in liquid form. Yet another object is to provide an improved polymeric composition that forms a solid matrix in situ thereby forming an implant for sustained release of a medicament over a desired period of time. A further object is to provide a liquid or solution polymeric composition that can form in situ a biodegradable solid or gelatinous drug delivery system wherein the amount and rate of the material delivered can be controlled, more precisely, especially when long-term release is required.